Identifying novel host cell receptors required for invasion by Trypanosoma cruzi metacyclic trypomastigotes

• Grant number: 14/19986-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2015
• End date: December 31, 2016
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Nobuko Yoshida
• Grantee: Louise Elizabeth Kemp
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

One of the fundamental questions about host cell invasion by Trypanosoma cruzi, that still awaits elucidation, refers to the identity of target cell receptors implicated in the process. Regarding metacyclic trypomastigotes, the parasite forms that initiate infection in the mammalian host, there is evidence that gp82, a stage-specific surface molecule, binds to target cells in a receptor-dependent manner. This binding triggers calcium signaling and lysosome exocytosis, events that are required for parasite internalization. Considering the importance of gp82 in cell invasion and in oral infection in mice, we aim to identify the receptor for gp82 that is present on human epithelial cells by employing two different strategies. The first involves the use of RNAi and the second is an unconventional strategy based on a preliminary observation that suggests that the receptor for gp82 may mimic a sequence of metacyclic form surface molecule gp90, which acts as a negative modulator of cell invasion. Initial results indicate that a monoclonal antibody directed to a cryptic epitope of gp90, which does not react with live metacyclic forms, apparently does recognize the host cell and inhibits parasite invasion. If it is confirmed that the receptor for gp82 has sequence similarity with gp90, the subsequent attempt at its identification could reveal a novel receptor, which would not be part of the repertoire of cell surface or cell associated components, such as extracellular matrix proteins, that have been described as relevant for invasion by tissue culture-derived trypomastigotes.